RESUMO
Metronidazole is a BCS (Biopharmaceutics Classification System) class 1 drug, traditionally considered the choice drug in the infections treatment caused by protozoa and anaerobic microorganisms. This study aimed to evaluate bioequivalence between 2 different marketed 250 mg metronidazole immediate release tablets. A randomized, open-label, 2×2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a 7-day washout period. The formulations were administered as single oral dose and blood was sampled over 48 h. Metronidazole plasma concentrations were determined by a liquid chromatography mass spectrometry (LC-MS/MS) method. The plasma concentration vs. time profile was generated for each volunteer and the pharmacokinetic parameters Cmax, Tmax, AUC0-t, AUC0-∞, ke, and t1/2 were calculated using a noncompartmental model. Bioequivalence between pharmaceutical formulations was determined by calculating 90% CIs (Confidence Intervall) for the ratios of Cmax, AUC0-t, and AUC0-∞ values for test and reference using log-transformed data. 22 healthy volunteers (11 men, 11 women; mean (SD) age, 28 (6.5) years [range, 21-45 years]; mean (SD) weight, 66 (9.3) kg [range, 51-81 kg]; mean (SD) height, 169 (6.5) cm [range, 156-186 cm]) were enrolled in and completed the study. The 90% CIs for Cmax (0.92-1.06), AUC0-t (0.97-1.02), and AUC0-∞ (0.97-1.03) values for the test and reference products fitted in the interval of 0.80-1.25 proposed by most regulatory agencies, including the Brazilian agency ANVISA. No clinically significant adverse effects were reported. After pharmacokinetics analysis, it concluded that test 250 mg metronidazole formulation is bioequivalent to the reference product according to the Brazilian agency requirements.
Assuntos
Antitricômonas/administração & dosagem , Metronidazol/administração & dosagem , Administração Oral , Adolescente , Adulto , Análise de Variância , Antitricômonas/efeitos adversos , Antitricômonas/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Método Duplo-Cego , Medicamentos Genéricos , Feminino , Humanos , Masculino , Espectrometria de Massas , Metronidazol/efeitos adversos , Metronidazol/farmacocinética , Pessoa de Meia-Idade , Padrões de Referência , Equivalência Terapêutica , Adulto JovemRESUMO
The occurrence of Escherichia coli O157:H7 was evaluated in 886 samples of hamburgers produced by eight manufacturers in the south and southeast of Brazil from January to September of 1997. The pathogen was not detected in any of the samples analyzed, although 17 (1.9%) showed the presence of E. coli strains, which presented agglutination with O157 antiserum. These strains were not confirmed, since a subsequent identification indicated that they were fermentation positive for sorbitol, incapable of agglutination with the antisera of other commercial brands, and nonproducers of verocytotoxins. A high rate of false-presumptive-positive tests was observed with strains of enterobacteria when isolated by the culture method and when using a commercially purchased enzymatic immunoassay. This high rate of false presumptive positives was likely because the initial screening for sorbitol-negative strains was carried out using phenol red sorbitol 4-methylumbelliferyl-beta-D-glucuronide agar, which was shown to be inadequate for this purpose.